(1) Field of the Invention
This invention concerns methods for identifying A2B adenosine receptor agonists and antagonists as well as methods for using A2B receptor antagonists to treat cell proliferation disorders mediated by the A2B adenosine receptor.
(2) Description of the Art
Adenosine is released by hypoxic tissues and is believed to be an angiogenic factor that links altered cellular metabolism caused by O2 deprivation to compensatory angiogenesis. Adenosine binds to four subtypes of G protein-coupled receptors termed A1, A2A, A2B and A3. The nucleoside adenosine has been implicated in angiogenesis. Specifically, it has been demonstrated that adenosine activation of the A2B adenosine receptor (AdoR) increased cAMP accumulation, cell proliferation and VEGF expression in human retinal endothelial cells (HREC). It has been previously reported that the activation of A2B AdoR increased vascular endothelial cell growth factor (VEGF) mRNA and protein expression in human retinal endothelial cells (HREC). Adenosine also has a synergistic effect with VEGF on retinal endothelial cell proliferation and capillary morphogenesis in vitro.
Microvascular abnormalities of the retina, such as retinopathy or prematurity, macular degeneration and diabetic retinopathy are among the leading causes of non-traumatic blindness. These diseases are characterized by neovascularization that results from ischemic injury to retinal vessels, i.e., compensatory angiogenesis. Thus one possible therapy for treating these diseases is to inhibit neovascularization.